Background/Aim: The frequency of sexual dysfunction (SD) is not well known in patients with chronic hepatitis C virus (HCV). In spite of the fact that histological benefits of peginterferon (Peg-IFN)/ribavirin therapy are well established, the effects on sexual health are less certain. To assess the prevalence of the SD and explore its relevance to histopathologic changes and Peg-IFN treatment. Materials and Methods: The study included 100 HCV males; all the patients completed questionnaires to assess their sexual function before and during the treatment. Results: Before treatment, SD was reported only by 12 (19.4%) and 10 (29.4%) patients of early and advanced liver fibrosis, respectively. SD during HCV treatment (with Peg-IFN and ribavirin) for liver fibrosis was significant, as 24 (70.6%) out of 34 (100%) of HCV patients had advanced fibrosis but only 20 (32.3%) out of 62 (100%) patients had early fibrosis and were sexually affected (P = 0.01). SD before treatment was found in 22 (22%) patients; 16 (16%) were >40 years old and 6 (6%) patients were ≤40 years old. SD showed highly significant (P = 0.001) difference prior to and during treatment. Pre treatment, 78 (78%) patients denied any SD and only 22 (22%) were sexually affected, while during treatment, the number of patients who were sexually affected rose to 44 (44%). The rest of the group [56 (56%)] did not report any sexual impairment. Conclusion: SD was noticed during Peg-IFN and ribavirin treatment in patients with advanced liver fibrosis. Age and advanced liver fibrosis were important factors in inducing SD. This is of key importance for clinical practice as it modifies the management of HCV patients.

Chronic hepatitis C virus (HCV) infection represents a major health problem and is estimated to affect 170 million persons worldwide. [1] Chronic viral hepatitis is typically silent; symptoms and signs are present only in those with severe or advanced disease. [2] Sexuality is an important aspect of the quality of life. Although sexual transmission has been an area of research in HCV positive patients, sexual functioning of these patients has received very limited attention. The frequency of sexual dysfunction (SD) is not well known in patients with chronic hepatitis C. [3] In spite of the fact that histological benefits of peginterferon (Peg-INF)/ribavirin therapy are well established, the effects on sexual health are less certain. [4] Common side effects of Peg-INF and ribavirin therapy include nonspecific symptoms such as fatigue, muscle aches, headaches, and low-grade fever; gastrointestinal symptoms of nausea, weight loss, and poor appetite; bone marrow effects such as anemia, neutropenia, and thrombocytopenia; and psychological difficulties such as anxiety, emotional lability, irritability, depression, and trouble in sleeping and concentration. Sexual side effects are infrequently mentioned complications of Peg-INF and ribavirin therapy. Rare instances of SD and impotence have been mentioned among treated patients and SD has been reported to be more common in patients with chronic hepatitis C than in persons without known liver disease. [5] Nevertheless, the sexual health of men with chronic hepatitis C before, during, and after combination therapy has not been well studied. [6]

Materials and Methods

We prospectively enrolled 100 males with chronic hepatitis C virus (HCV). Before the treatment and at 4, 12, 24 and 48 weeks of therapy, all the patients completed questionnaires (derived from validated questionnaires) about sexual desire; erection, ejaculation, sexual problem assessment and overall sexual satisfaction (see below) to assess their sexual function. All our patients were confirmed to have chronic HCV by full history taking, HCV antibody test, HCV RNA PCR and liver biopsy. Patients who were treated with Pre-Peg-IFN and ribavirin and those with thyroid dysfunction, diabetes, and hypertension were excluded. Patients with symptoms of depression or anxiety were excluded from the study.

Sexual health questionnaires

Five sexual health questions (Q1-Q5), each with five levels of response, were derived from validated questionnaires used to evaluate sexual health in patients and the effects of medications on sexual desire, function, and satisfaction. [7],[8]

Q1. Over the past month, how often have you felt sexual desire?

1. Almost always or always, 2. Most times (more than half the time), 3. Sometimes (about half the time), 4. A few times (less than half the time), 5. Never.

Q2. Over the past month, how often were you able to get an erection during sexual activity?

0. No sexual activity, stimulation or intercourse, 1-5 (same options as in Q1).

Q3 Over the past month, when you had sexual stimulation or intercourse, how often did you ejaculate?

0. No sexual activity, stimulation or intercourse, 1-5 (same options as in Q1).

Q4. Over the past month, how satisfied have you been with your overall sexual life?

1. Much better, 2. Somewhat better, 3. About the same, 4. Somewhat worse, 5. Much worse? (This question was not asked before treatment).

For analysis, the degree of sexual dysfunction or impairment was categorized as none, mild, moderate or severe (Q1-Q4) or as better, the same or worse (Q5) based upon responses to the five questions. Impaired sexual desire (Q1) was categorized as "none" (response categories 1 or 2), "mild" (Q3), "moderate" (Q4), or "severe" (Q5); erectile dysfunction (Q2), ejaculatory dysfunction (Q3), and global dissatisfaction (Q4) as "none" (1), "mild" (2), "moderate" (3), or "severe" (4 or 5); and, global deterioration (Q5) as "better" (1 or 2), "the same" (3), and "worse" (4 or 5).

Liver biopsy methodology

After taking informed consent, liver biopsy was performed for the 100 patients using 16-gauge true-cut needles and was scored using Metavir scoring system for both inflammation and fibrosis. All liver biopsies were interpreted; the scoring consists of using a grading and a staging system. The grade gives an indication of the activity or amount of inflammation, and the stage represents the amount of fibrosis or scarring. The grade was scored from 0 to 3 (0 = no activity, 1 = mild, 2 = moderate, and 3 = severe activity). The degree of inflammation is important because it is considered a precursor to fibrosis. The fibrosis score was assigned a number from 0 to 4 (0 = no scarring, 1 = minimal scarring corresponding to stellate enlargement of portal tracts without septae formation, 2 = enlargement of portal tracts with rare septae formation, 3 = numerous septae without fibrosis, 4 = cirrhosis or advanced scarring of the liver). Patients graded ≥A2 and/or ≥F2 were considered to have significant pathology. [9]

Statistical analysis

Data were analyzed using SPSS win statistical package version 15. Numerical data were expressed as mean ± SD. Qualitative data were expressed as frequency and percentage. Chi-square test (or Fisher's exact test) was used to examine the relation between qualitative variables. McNemar test was used to examine the change of repeated qualitative variables. For quantitative data, comparison between two groups was done using Mann-Whitney test. P-value less than 0.05 were considered significant.

Results

Baseline characteristics are shown in [Table 1]. All patients were males with mean [standard deviation (SD)] age 41.4 years (10.9), BMI (s.d.) 26.1 (4.1) and HCV viremia of 1,445,290 (s.d.) (5,081,127) IU/ml. SD prior to the treatment was in 22 (22%) patients; out of them, 20 (20%) were mildly and 2 (2%) were moderately affected while none of the patients were affected severely. With the treatment, the SD was mild in 20 (20%), moderate in 18 (18%) and severe in 6 (6%) patients. The mean histological activity grades were as follows: Mild 64 (64.0%), moderate 22 (22.0%) and severe 14 (14.0%), and there were no fibrosis in 4 (4%), early fibrosis in 62 (62.0%) and advanced fibrosis was in 34 (34.0%) patients.

[Table 2] shows that there was no significant relation between SD and the degree of necro-inflammatory activity prior to the treatment. SD was found in 14 (21.9%), 4 (18.2%) and 4 (28.6%) patients of mild, moderate and severe necro-inflammatory activity, respectively.

[Table 3] shows that before treatment, SD was found only in 12 (19.4%) and 10 (29.4%) patients of early and advanced liver fibrosis, respectively. SD during HCV treatment (with Peg-IFN and ribavirin) for liver fibrosis was significant, as 24 (70.6%) out of 34 (100%) of HCV patients had advanced fibrosis, but only 20 (32.3%) out of 62 (100%) patients had early fibrosis and were sexually affected (P = 0.01) [Table 4] and [Figure 1], whereas the effect of treatment on HCV patients with regard to their necro-inflammatory activity grades showed no significant differences in their sexual function. SD was reported by 24 (37.5%), 12 (54.5%) and 8 (57.1%) patients of mild, moderate and severe necro-inflammatory activity [Table 5].

SD during treatment was highly significantly affected (P = 0.001) in those belonging to age group more than 40 years in comparison with those of 40 years or less. In patients more than 40 years, SD was mildly affected in 38 (73.1%), moderately affected in 16 (30.8%), and severely affected in 6 (11.5%) patients. On the other hand, in the age group of ≤40 years, only 6 (12.5%) were sexually affected, 4 (8.3%) were mildly affected and 2 (4.2%) were moderately affected, but no one (0%) was severely sexually affected [Table 6] and [Table 7] and [Figure 2]. SD before treatment was found in 22 (22%) patients; 16 (16%) were more than 40 years old and 6 (6%) patients were ≤40 years old. SD showed highly significant (P = 0.001) difference prior to and during treatment. Before treatment, 39 (78%) denied having any SD and only 22 (22%) were sexually affected. While during treatment, the number of patients who were sexually affected rose to 44 (44%). The rest of the group [56 (56%)] did not report any sexual impairment [Table 8]. The patients who had sexual complaints before the treatment continued to complain with the same degree during treatment (10%) (eight mild and two moderate), while 12% of patients deteriorated sexually (6 changed from mild to moderate and 6 from mild to severe). The rest of the group started to complain during the treatment; there were 12 patients who were mildly affected and 10 who were moderately affected and no one reported severe sexual impairment [Table 1].

Sexual function and health are the important elements in determining the quality of life and overall well-being of a person. In our study, some degree of impairment in sexual desire was reported in 22% of male HCV patients before therapy. Progressive worsening in patient's sex life after therapy was noticed in 44% patients. This coincides with the findings of Dove et al.[6] who obtained almost the same results on SD, in spite of the fact that Dove's study included a larger number (260) of male American patients (Caucasians and Africans) with BMI 28.5 and age 48 years (43-48 years), our study included 100 HCV Egyptian patients with BMI 26.1 and mean age of 41.4 years. In addition, we observed a decline in the SD during therapy only in 12/22 (54.5%) patients who suffered before the treatment. Dove et al., [6] reported significant declines in all components of sexual health during therapy. We observed in our study that SD (16%) correlated with age. Similarly, Soykan et al.[3] reported that SD correlated with age (P < 0.07) and Dove et al.[6] found significant difference (P < 0.05) of SD compared to age. This may be because Dove et al. included older patients in their study (patients' age was between 18 and 70 years), but in our study the ages ranged from 18 to 60 years (mean age 41.4 years). Soykan et al. [3] admitted that there was SD in 21% of his chronic HCV patients; the mean age of his patients was 46.4 years, which coincides with the findings of our study. Moreover, Danoff et al. and Foster [10],[11] reported in accordance with our results strong association between sexual dysfunction and advanced hepatic fibrosis or cirrhosis. In our study, more SD was found during Peg-IFN and ribavirin treatment in patients with advanced liver fibrosis, and it appeared that age was the most important factor and advanced liver fibrosis was an important independent co-factor in inducing SD during treatment. Thus, one cannot claim with confidence that the relatively high rates of SD in these HCV patients (44% reported moderate to severe dissatisfaction with their sexual life) were higher than expected in men of similar age and race without liver disease.

Conclusion

SD is a common side effect of Peg-IFN and ribavirin treatment, especially in middle-aged men. In addition, advanced liver fibrosis is an important co-factor in inducing SD during treatment. This finding could be of key importance for the clinical practice because it could modify the current management of HCV patients. Therefore, chronic HCV patients treated with Peg-IFN and ribavirin should be warned against the possibility of SD, especially if they are middle aged or having advanced liver fibrosis.